The Neurocritic

Friday, April 29, 2011

Obsessive compulsive disorder (OCD) is a mental illness characterized by unwanted and intrusive thoughts, feelings, or ideas (obsessions), and ritualized behaviors (compulsions) the individual feels driven to perform in order to alleviate the disturbing nature of the obsessions. It is a major anxiety disorder classified in Axis I of the DSM-IV, which can be disabling to those who suffer with it.

The specific symptoms of OCD can include fear of contamination (from germs and physical contact with others) and resultant pathological cleaning rituals, fear of causing catastrophic harm to others, disturbing "impure thoughts" often of a sexual nature, and compulsive ordering, organization, and checking.

Currently, major treatments for OCD include cognitive behavior therapy (CBT), considered to be...

...the most effective type of psychotherapy for this disorder. The patient is exposed many times to a situation that triggers the obsessive thoughts, and learns gradually to tolerate the anxiety and resist the urge to perform the compulsion. Medication and CBT together are considered to be better than either treatment alone at reducing symptoms.

However, a new study by Koçak et al. (2011) has expanded the range of cognitive processes and brain regions that might be implicated in OCD. The authors proposed that since OCD patients are quite impaired at suppressing complex thoughts and intrusive images, they might also show deficits in suppressing very simple, neutral images and shapes.

Participants in their fMRI experiment were 12 patients with OCD [eight were cleaners, three were checkers (one of the checkers also had contamination obsessions), and one had harming obsessions] and 12 age-matched controls. The tasks performed in the scanner involved forming a visual mental image of a geometric shape and then manipulating this visual image. Three of the tasks involved cognitive control over visual imagery (imagination, suppression, and erasing) and two were baseline tasks (free imagination, resting). Before the scanning session, participants studied the shape until they were able to draw it from memory.

Fig. 1. (Koçak et al., 2011). The shape shown to the participants. The arrow (which did not appear on the paper used in the study) indicates the starting point of the erasing task. The participants were instructed to begin erasing the shape at the point indicated by the arrow and to continue until the shape completely disappeared.

The instructions given to the participants for these tasks were as follows: 1. Imagination task: imagine the shape on the paper continuously until another command is given; 2. Suppression task: imagine the paper with the shape on it immediately after the command is given, and then immediately suppress the image of the shape (try to see the paper as blank) until another command is given; 3. Erasing task: imagine the paper with the shape on it, and then erase the shape by tracing its outline it until another command is given; 4. Free-imagination task; imagine whatever comes to mind and change it with any other intrusive image – a type of free-association task of mental images (this task was used as the baseline condition task); 5. Resting condition: rest while in the scanner.

Since the tasks involved imagery alone and no overt responding, the only measures of performance were the participants' subjective evaluation of how well they were able to continually perform each task during the 25 sec blocks. The OCD group claimed they performed the suppression task better than controls, but we have no external way to validate this finding.

Turning to the neuroimaging results, the major contrasts were the three active imagery tasks, each compared to the free-imagination baseline task. The group comparison across the three active tasks (which did not differ from each other) is shown below.

Individuals with OCD showed less activation than controls in three regions in the right hemisphere: the superior frontal gyrus,1 the inferior parietal lobe, and the posterior cingulate cortex[part of the default mode network]. The right IPL is very important for visuospatial processing (Verden et al., 2010); OCD patients can exhibit visuospatial impairments. Furthermore, activations in both IPL and PCC have been observed in prior studies of visual imagery (Ganis et al., 2004). If the participants with OCD were less adept at imagining, manipulating and suppressing a geometric shape, perhaps this reflects a deficit in imagery that is much more basic than controlling the contents of thought.

Although these results are very preliminary, the idea that obsessive thoughts could be associated with problems in the right parietal lobe and control over visual mental imagery is intriguing. One might speculate that repeated practice at generating and then suppressing simple geometric figures could potentially benefit many individuals with OCD, who must cope with disturbing and intrusive images on a daily basis.

Footnote

1 One potential confound that is not discussed is possible differences in eye movements between the groups. The participants were instructed to keep their eyes closed, but of course that didn't prevent them from moving their eyes. However, the activated SFG area in this experiment is anterior to the frontal eye fields, and the IPL region is lateral to a saccade-sensitive area in the IPS. Also, it's not clear why the activations would be right lateralized.

Friday, April 22, 2011

A study on electrophysiological recordings from single neurons in the dorsolateral prefrontal cortex of two monkeys trained to perform a visual target discrimination task (Lennert & Martinez-Trujillo, 2011) has supposedly given new hope to patients with a diverse array of neurological and psychiatric conditions, according to a press release:

ScienceDaily (Apr. 19, 2011) — Until now, it has been assumed that people with conditions like ADHD, Tourette syndrome, obsessive compulsive disorder and schizophrenia -- all of whom characteristically report symptoms of "brain clutter" -- may suffer from anomalies in the brain's prefrontal cortex.

Damage to this brain region is often associated with failure to focus on relevant things, loss of inhibitions, impulsivity and various kinds of inappropriate behaviour. So far, exactly what makes the prefrontal cortex so essential to these aspects of behaviour has remained elusive, hampering attempts to develop tools for diagnosing and treating these patients.

But new research by Julio Martinez-Trujillo, a professor in McGill University's Department of Physiology and Canada Research Chair in Visual Neuroscience, has brought new hope to these patients. He believes the key to the "brain clutter" and impulsivity shown by individuals with dysfunctional prefrontal cortices lies in a malfunction of a specific type of brain cell. Martinez-Trujilo and his team have identified neurons in the dorsolateral sub-region of the primate prefrontal cortex that selectively filter out important from unimportant visual information. The key to the normal functioning of these "filter neurons" is their ability to, in the presence of visual clutter, selectively and strongly inhibit the unimportant information, giving the rest of the brain access to what is relevant.

I am so flabbergasted by the number of misleading statements that I don't know where to begin. Let's take them in the order of occurrence.

"Until now" - This phrase implies that the study has refuted the assumption that ADHD, Tourette's, OCD, and schizophrenia are all associated with abnormalities in the prefrontal cortex (PFC). In fact, individuals with these disorders (and their PFCs) were not evaluated.

"brain clutter" - What does this mean? I'm not familiar with it as a technical term, nor how the phenomenon is manifest in all four of the above disorders. This issue is relatively minor.

"anomalies in the brain's prefrontal cortex" - The human PFC covers a large and diverse area of the brain.

Neuroimaging findings in ADHD, Tourette's, OCD and schizophenia are not uniform, and the implicated subregions of PFC are not the same. For example, OCD has been associated with overactivity in the orbitofrontal cortex (Menzies et al., 2008) while schizophrenia is associated with altered activation of dorsolateral PFC (Volk & Lewis, 2010).1

This is highly relevant because as we'll see, the monkey neurons under investigation were in a specific region analogous to Brodmann area 46 in human dorsolateral PFC.

"Damage to this brain region" and the subsequent laundry list of altered behaviors - not all associated with damage to BA 46.

"brought new hope to these patients" - This is by far the most egregious falsehood of the entire press release. I find it to be utterly irresponsible.

None of these claims were made in the paper itself, which examined firing rates of neurons in the principal sulcus of two rhesus macaque monkeys trained to perform a color-rank target discrimination task with moving random dot patterns.

Figure adapted from the press release. The pinkish highlighted area of the brain is the principal sulcus region where neuron activity was recorded.

The authors summarize the results below. You'll notice there's no mention of developing "tools for diagnosing and treating these patients" or bringing "new hope to these patients."

Wednesday, April 20, 2011

Emoticons – The emotional meaning of form, shape & music is a multimedia project of Kallbrand that explores design and emotion. The four basic emoticons -- rapture, dread, repose, and despondence -- are classified along the dimensions of valence (positive, negative) and intensity (high, low). Each of these emotions is associated with specific shapes, forms, music, colors, and... chairs.

This is the “despondence” object emoticon. The despondence emoticon chair is designed to have the properties found to evocate emotions pertaining to the low intensity/negative valence area of emotion. The despondence emoticon chair is designed to be 3D printed in a composite plastic resin which is then cured into one solid piece. This allows for very complex organic surfaces with fluid surface continuity in all directions whilst at the same time enabling a rough, crackled texture to be physically modeled right into the form. ... The overall shape becomes very visually unbalanced because of the lack of a unified direction in the parts and by their differences in thickness and weight. Since the seat is leaning forward, you are always about to slip off, which naturally makes sitting in the chair feel quite discomfortable. This imbalance symbolize an unsettled emotional state.

Psychologist Paul Ekman is known for his work on the facial expression of emotion [and also for his role as scientific consultant for the TV show Lie to Me]. His original finding was that there are six universal emotions: anger, fear, disgust, surprise, happiness, and sadness (Ekman & Friesen, 1969).

Wednesday, April 13, 2011

Restless legs syndrome (RLS) is a neurological disorder characterized by throbbing, pulling, creeping, or other unpleasant sensations in the legs and an uncontrollable, and sometimes overwhelming, urge to move them. Symptoms occur primarily at night when a person is relaxing or at rest and can increase in severity during the night. Moving the legs relieves the discomfort. Often called paresthesias (abnormal sensations) or dysesthesias (unpleasant abnormal sensations), the sensations range in severity from uncomfortable to irritating to painful.

RLS is a relatively common movement disorder that affects ~2.7% of the population (Earley & Silber, 2010). RLS might be related to dysfunction in basal ganglia circuits that use dopamine, which is needed to produce smooth, purposeful muscle activity and movement. Disruption of these BG circuits can produce involuntary movements. Thus, dopaminergic drugs such as pramipexole and ropinirole are often used for treatment, but these medications can produce unwanted side effects.

A case study in the journal Sleep Medicine (Marin et al., 2011) reported on a patient who found his own method for the relief of his persistent RLS:

Restless legs syndrome (RLS) is a distressing neurologic condition characterized by urgency to move the legs usually associated with unpleasant sensations in the lower limbs. The symptoms are worst at night and at rest, and patients must move their legs or walk to get relief from their symptoms. Herein, we report a 41-year-old man with a history of severe RLS for 10 years causing him difficulty falling asleep and staying asleep. He fulfilled the four essential criteria established by the International RLS Study Group and he scored 32 in the International RLS Rating Scale. The patient reported that he would get complete relief from RLS symptoms, granting him a normal sleep following sexual intercourse or masturbation. Pramipexole was introduced 2 h before bedtime with significant improvement of RLS symptoms, but whenever he was without medication, he returned to sexual behavior to get relief from RLS symptoms.

There are anecdotal reports that sexual activity and orgasm may relieve RLS symptoms, although in some cases sexual activity may worsen RLS. One may speculate that the release of orgasm-related dopamine and opioid may play a role in the relief of RLS symptoms. Additionally, there is a previous report of a RLS patient showing repetitive, rhythmic pelvic body movements resembling coital behavior at the wake–sleep transition.

Friday, April 08, 2011

This sums up the basic conclusion of a new study on political orientation and brain structure by Ryota Kanai, Tom Feilden, Colin Firth and Geraint Rees in the journal Current Biology. Yes, that Colin Firth...

Science correspondent Tom Feilden: "What started out as a bit of fun has turned into quite a significant piece of science."

Scientific research commissioned by this programme on behalf of our guest editor, Colin Firth, has shown a strong correlation between the structure of a person's brain and their political views.

You can also listen to a brief audio clip of Feilden discussing the study at the link above. Firth actually commissioned Professor Geraint Rees at University College London to obtain structural MRI scans from two diametrically opposed politicians: conservative MP Alan Duncan (a member of the Conservative Party) and liberal MP Stephen Pound (a member of the Labour Party).

Feilden then asks a question that is unanswerable from studying brain structure in adults: "Are political beliefs learnt, the product of experiences in our environment, or 'hard wired' in the brain?" Since a comparison of n=1 liberal versus n=1 conservative is not scientifically valid, Rees went back to a database of MRI scans from UCL students and asked these participants about their political beliefs. Feilden then discussed the results before the paper had been formally submitted for publication [according to the journal website, the paper was received by Current Biology on 11 January, 2011]. Briefly, he said that the gray matter of the anterior cingulate cortex was thicker among the liberal or left wing participants while the amygdala was much larger in those who identified as conservative or right wing.

"But is it cause and effect?" asks an interviewer. Rightfully so. Correlation does not equal causation. Then there's the claim that the structural brain variation means the political differences are "hard wired". The observed anatomical differences prove no such thing. Any experience will change the brain in some way, and repeated patterns of behavior, whether it's learning to juggle or voting conservative due to a certain set of core beliefs, can alter the brain. Nonetheless, we have the following headline:

"Give me the child until he's seven and I'll give you the man."It's clear from their motto that the Jesuits are firmly in the acquired camp when it comes to whether our political beliefs and values are learned or hard wired from birth: the product of experience rather than genetics.But is that true?

...along with the eventual admission:

Although the results do show that political belief is reflected in the physical structure of the brain it's not clear which comes first. Whether the structure of the brain shapes political belief or political belief leads to the differential development of brain structure.

All right, that was a media stunt, you say -- but how about the peer reviewed paper (Kanai et al., 2011)?

A total of 90 healthy middle-class to upper-class participants (mean age = 23.5 yrs) underwent MRI scanning and [later?] filled out a very brief questionnaire on their political views:

Participants were asked to indicate their political orientation on a five-point scale of very liberal (1), liberal (2), middle-of-the-road (3), conservative (4), and very conservative (5). ... Because none of the participants reported the scale corresponding to very conservative, the analyses were conducted using the scales of 1, 2, 3, and 4.

If I'm not mistaken, no special effort was made to recruit very conservative participants, because the study was conceived after the MRIs were obtained.

As reported by Feilden, being liberal was associated with a larger anterior cingulate whereas being conservative was associated with a larger right amygdala1 (see Figure 1 below).

Figure 1 (Kanai et al., 2011). Individual Differences in Political Attitudes and Brain Structure. (A) Regions of the anterior cingulate where gray matter volume showed a correlation with political attitudes are shown overlaid on a T1-weighted MRI... A statistical threshold of p < 0.05, corrected for multiple comparisons, is used for display purposes. The correlation (left) between political attitudes and gray matter volume (right) averaged across the region of interest (error bars represent 1 standard error of the mean, and the displayed correlation and p values refer to the statistical parametric map presented on the right) is shown. (B) The right amygdala also showed a significant negative correlation between political attitudes and gray matter volume. Display conventions and warnings about overinterpreting the correlational plot (left) are identical to those for (A).

The results were based on measurements of gray matter density in these two specific structures. How were they chosen? First, the anterior cingulate was selected based on the finding of Amodio et al. (2007) that...

...the amplitude of event-related potentials reflecting neural activity associated with conflict monitoring in the anterior cingulate cortex (ACC) is greater for liberals compared to conservatives. Thus, stronger liberalism is associated with increased sensitivity to cues for altering a habitual response pattern and with brain activity in anterior cingulate cortex.

I had issues with this interpretation of the Amodio et al. study in 2007, which I will summarize here. One problem was attributing the observed results to political viewpoint and not to other factors. The study used EEG recordings, specifically event-related potentials. The ERP brain waves reflect electrophysiological activity recorded remotely from the scalp. While it's great for determining the temporal parameters of neural activity, it's not so great at determining where the activity is located in the brain.

One brain wave of interest was the error-related negativity (ERN), recorded at the time that people make mistakes in a task:

The response-locked error-related negativity (ERN), which peaks at approximately 50 ms following an incorrect behavioral response, reflects conflict between a habitual tendency (for example, the Go response) and an alternative response (for example, to inhibit behavior in response to a No-Go stimulus).

However, it's not at all clear that ERN reflects conflict-monitoring (Carbonnell & Falkenstein, 2006). Thus, based on a smaller-sized ERN in conservatives, one cannot conclude that they are "less responsive to conflict." In fact, if one wants to apply the logic of conflict monitoring to political viewpoint, one could say that conservatives might be more freaked out by ambiguity and conflict, since it violates their simplistic world view. Although liberals did indeed show larger ERN waves than conservatives when making mistakes, so do individuals with clinical diagnoses such as obsessive-compulsive disorder (Gehring et al., 2000) or major depressive disorder (Chiu & Deldin, 2007). So we can't dismiss the possibility that the liberals might have been more depressed or obsessive compulsive than the conservatives.

Back to the present day, the specific ACC region of interest (ROI) was chosen from an fMRI study [not the EEG study, which has lower spatial resolution] entitled, "A midline dissociation between error-processing and response-conflict monitoring" (Garavan et al., 2003). Garavan and colleagues found that different locations in the medial frontal cortex responded preferentially to error processing (the ACC ROI selected by Kanai et al., 2011) and to conflict monitoring (a more posterior and dorsal region called the pre-SMA). However, Kanai and colleagues concluded:

Thus, it is conceivable that individuals with a larger ACC have a higher capacity to tolerate uncertainty and conflicts, allowing them to accept more liberal views. Such speculations provide a basis for theorizing about the psychological constructs (and their neural substrates) underlying political attitudes. However, it should be noted that every brain region, including those identified here, invariably participates in multiple psychological processes. It is therefore not possible to unambiguously infer from involvement of a particular brain area that a particular psychological process must be involved.

But it seems to me that if you want to say "a higher capacity for conflict correlates with a larger X brain region", based on Garavan et al. you'd have to choose the pre-SMA and not the ACC.

It's an appealing story and a topic worth investigating, says cognitive neuroscientist Martha Farah of the University of Pennsylvania. But there's plenty of reason to be cautious, she says. For one, it's not clear what a bigger amygdala—or a bigger anything in the brain—actually means in terms of brain function and behavior. The research, she says, is unclear and often contradictory on this point.

Another problem is that most brain regions have multiple functions, Farah says: "Who says fear is the only function of the amygdala?" She notes that this brain region also responds to sexually arousing images and pictures of happy faces, and one recent study found a correlation between amygdala volume and the size of people's social networks. Likewise, the anterior cingulate cortex has been implicated in a long list of cognitive functions. By picking and choosing from the previous studies, "they're indulging in a bit of just-so storytelling," Farah says.

After all this criticism, I have to point out an impressive aspect of the paper, and that is the replication of results in an independent group of 28 participants. In the end, I don't doubt that there are differences between the brains of liberal and conservative people. But how they got that way, and what it means, are questions for further investigation.

Footnote

1 Why only the right amygdala and not the left? The authors didn't provide an explanation.

Saturday, April 02, 2011

The 18th Annual CNS Meeting is being held in San Francisco April 2-5, 2011. Grueling 11 hr days of posters and talks (plus late night revelry) await the most eager attendees with the greatest stamina. Symposia include panels of Psychological Constructionists, Angular Gyrus Devotees, Fans of Human Consumption, Brainy Bilinguals, and Multimodal Person Perceivers.

Cognitive neuroscience has traditionally sought the distinct neural bases of psychological categories like “thought,” “attention,” “memory” and “emotion.” Yet growing evidence suggests that the mechanisms underlying these psychological categories are not as distinct as once thought. According to a psychological constructionist framework, complex mental categories are phenomena constructed from more basic psychological ingredients that correspond to functional networks in the brain. In this symposium, we will explore how a psychological constructionist approach to the mind can inform cognitive neuroscience. The four talks presented will be empirical examples of a psychological construction approach. Kristen Lindquist will present meta-analytic data demonstrating that emotion experiences and perceptions are comprised of activity in functional groupings associated with affect, categorization, language and executive attention. Next, Tor Wager will present findings demonstrating that the same basic brain system is involved in functions central to the “self,” pain, and negative emotion. William Cunningham will next demonstrate how amygdala activity is dynamically shaped by the goals of a perceiver. Finally, Alexandra Touroutoglou will next present evidence demonstrating that both attention and emotion experience have a common ingredient in the anterior insula.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.